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Clinical course impacts early kinetics,magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection.

ABSTRACT: To understand the determinants of long-term immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the concurrent impact of vaccination and emerging variants, we follow a prospective cohort of 332 patients with coronavirus disease 2019 (COVID-19) over more than a year after symptom onset. We evaluate plasma-neutralizing activity using HIV-based pseudoviruses expressing the spike of different SARS-CoV-2 variants and analyze them longitudinally using mixed-effects models. Long-term neutralizing activity is stable beyond 1 year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while the responses of non-hospitalized individuals are dominated by long-lived B cells. In both groups, vaccination boosts responses to natural infection. Long-term (>300 days from infection) responses in unvaccinated participants show a reduced efficacy against beta, but not alpha nor delta, variants. Multivariate analysis identifies the severity of primary infection as an independent determinant of higher magnitude and lower relative cross-neutralization activity of long-term neutralizing responses.

SUBMITTER: Pradenas E

PROVIDER: S-EPMC8784437 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Clinical course impacts early kinetics,magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection.

Pradenas Edwards E Trinité Benjamin B Urrea Víctor V Marfil Silvia S Tarrés-Freixas Ferran F Ortiz Raquel R Rovirosa Carla C Rodon Jordi J Vergara-Alert Júlia J Segalés Joaquim J Guallar Victor V Valencia Alfonso A Izquierdo-Useros Nuria N Noguera-Julian Marc M Carrillo Jorge J Paredes Roger R Mateu Lourdes L Chamorro Anna A Toledo Ruth R Massanella Marta M Clotet Bonaventura B Blanco Julià J

Cell reports. Medicine 20220124 2

To understand the determinants of long-term immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the concurrent impact of vaccination and emerging variants, we follow a prospective cohort of 332 patients with coronavirus disease 2019 (COVID-19) over more than a year after symptom onset. We evaluate plasma-neutralizing activity using HIV-based pseudoviruses expressing the spike of different SARS-CoV-2 variants and analyze them longitudinally using mixed-effects mod ...[more]

PMID: 35233547

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Project description:Viral populations in natural infections can have a high degree of sequence diversity, which can directly impact immune escape. However, antibody potency is often tested in vitro with a relatively clonal viral populations, such as laboratory virus or pseudotyped virus stocks, which may not accurately represent the genetic diversity of circulating viral genotypes. This can affect the validity of viral phenotype assays, such as antibody neutralization assays. To address this issue, we tested whether recombinant virus carrying SARS-CoV-2 spike (VSV-SARS-CoV-2-S) stocks could be made more genetically diverse by passage, and if a stock passaged under selective pressure was more capable of escaping monoclonal antibody (mAb) neutralization than unpassaged stock or than viral stock passaged without selective pressures. We passaged VSV-SARS-CoV-2-S four times concurrently in three cell lines and then six times with or without polyclonal antiserum selection pressure. All three of the monoclonal antibodies tested neutralized the viral population present in the unpassaged stock. The viral inoculum derived from serial passage without antiserum selection pressure was neutralized by two of the three mAbs. However, the viral inoculum derived from serial passage under antiserum selection pressure escaped neutralization by all three mAbs. Deep sequencing revealed the rapid acquisition of multiple mutations associated with antibody escape in the VSV-SARS-CoV-2-S that had been passaged in the presence of antiserum, including key mutations present in currently circulating Omicron subvariants. These data indicate that viral stock that was generated under polyclonal antiserum selection pressure better reflects the natural environment of the circulating virus and may yield more biologically relevant outcomes in phenotypic assays. Thus, mAb assessment assays that utilize a more genetically diverse, biologically relevant, virus stock may yield data that are relevant for prediction of mAb efficacy and for enhancing biosurveillance.

Project description:To assess the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced by natural infection and describe the serological characteristics over 7 months after symptom onset among coronavirus disease 2019 (COVID-19) patients by age and severity group, we followed up COVID-19 convalescent patients confirmed from 1 January to 20 March 2020 in Jiangsu, China and collected serum samples for testing IgM/IgG and neutralizing antibodies against SARS-CoV-2 between 26 August and 28 October 2020. In total, 284 recovered participants with COVID-19 were enrolled in our study. Patients had a mean age of 46.72 years (standard deviation [SD], 17.09), and 138 (48.59%) were male. The median follow-up time after symptom onset was 225.5 (interquartile range [IQR], 219 to 232) days. During the follow-up period (162 to 282 days after symptom onset), the seropositive rate of IgM fluctuated around 25.70% (95% confidence interval [CI], 20.72% to 31.20%) and that of IgG fluctuated around 79.93% (95% CI, 74.79% to 84.43%). Of the 284 patients, 64 participants were tested when discharged from hospital. Compared with that at the acute phase, the IgM/IgG antibody levels and IgM seropositivity have decreased; however, the seropositivity of IgG was not significantly lower at this follow-up (78.13% versus 82.81%). Fifty percent inhibitory dilution (ID50) titers of neutralizing antibody for samples when discharged from hospital (geometric mean titer [GMT], 82; 95% CI, 56 to 121) were significantly higher than those at 6 to 7 months after discharge (GMT, 47; 95% CI, 35 to 63) (P < 0.001). After 7 months from symptom onset, the convalescent COVID-19 patients continued to have high IgG seropositive; however, many plasma samples decreased neutralizing activity. IMPORTANCE The long-term characteristics of anti-SARS-CoV-2 antibodies among COVID-19 patients remain largely unclear. Tracking the longevity of these antibodies can provide a forward-looking reference for monitoring COVID-19. We conducted a comprehensive assessment combining the kinetics of specific and neutralizing antibodies over 7 months with age and disease severity and revealed influencing factors of the protection period of convalescent patients. By observing the long-term antibody levels against SARS-CoV-2 and comparing antibody levels at two time points after symptom onset, we found that the convalescent COVID-19 patients continued to have a high IgG seropositive rate; however, their plasma samples decreased neutralizing activity. These findings provide evidence supporting that the neutralizing activity of SARS-CoV-2-infected persons should be monitored and the administration of vaccine may be needed.

Dataset Information

Clinical course impacts early kinetics,magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection.

Publications

Clinical course impacts early kinetics,magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection.

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